Resveratrol derivative production by high-pressure treatment: proliferative inhibitory effects on cervical cancer cells

  • Yuki Sugahara Graduate School of Integrated Pharmaceutical and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan
  • Toshiro Ohta Graduate School of Integrated Pharmaceutical and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan
  • Yoshiki Taguchi Graduate School of Integrated Pharmaceutical and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan
  • Sari Honda Graduate School of Integrated Pharmaceutical and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan
  • Yasuhiro Kashima UHA Mikakuto Co., Ltd., Osaka, Japan
  • Taiji Matsukawa UHA Mikakuto Co., Ltd., Osaka, Japan
  • Shigenori Kumazawa Graduate School of Integrated Pharmaceutical and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan
  • Wataru Kadowaki Graduate School of Integrated Pharmaceutical and Nutrition Sciences, University of Shizuoka, Shizuoka, Japan
Keywords: Food processing; Caffeic acid; Apoptosis; HeLa; PARP; p38


Background: In recent years, functional food components have attracted considerable attention. Resveratrol, a food polyphenol, has been widely studied due to its various physiological activities. Previously, we identified a novel resveratrol derivative, named RK4, in food, which is formed by a chemical reaction involving resveratrol and caffeic acid. Furthermore, it was suggested that high-pressure treatment is an important factor in RK4 production.

Objectives: The purpose of this study was to clarify relationships between high-pressure processing and component production and to compare RK4 with the known functional ingredient resveratrol to examine the physiological value of RK4. Through this research, we aimed to develop high-pressure treatment technology that adds new usefulness for food.

Methods: Resveratrol and caffeic acid were reacted under high-pressure treatment and in various conditions of concentration and temperature. RK4 levels in the reaction solution were quantitatively analyzed using liquid chromatography-mass spectrometry. In addition, HeLa cervical cancer cells were exposed to RK4 and resveratrol, and survival rates were measured using the methyl thiazolyl tetrazolium (MTT) method after culturing for 24 h. Activation of an apoptosis-inducing marker was detected by western blotting of cells cultured for 48 h after addition of the test compounds.

Results: By reacting resveratrol and caffeic acid under high-pressure conditions (~100 MPa), the amount of RK4 produced was significantly increased. It was also found that the reaction temperature and time contributed to this reaction. RK4 exhibited stronger cytotoxicity to HeLa cells than resveratrol. It was also shown that RK4 activated p38, cleaved poly ADP ribose polymerase, and induced apoptosis.

Conclusions: RK4 is a valuable component for further research as a novel compound with wider functionality than that of resveratrol. High-pressure treatment may substantially contribute to the production of novel food ingredients. Further elucidation of the relationships between high-pressure treatment and production of new ingredients has promising potential to guide development of new applications in food processing.


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How to Cite
Sugahara Y., Ohta T., Taguchi Y., Honda S., Kashima Y., Matsukawa T., Kumazawa S., & Kadowaki W. (2022). Resveratrol derivative production by high-pressure treatment: proliferative inhibitory effects on cervical cancer cells. Food & Nutrition Research, 66.
Original Articles